The spacecraft served as the crew's lifeboat while docked to the ISS. The Expedition 1 crew were returned to Earth via a Space Shuttle during STS-102 in March 2001, and the Soyuz TM-31 spacecraft stayed with the station for part of Expedition 2. In April 2001 another spacecraft, Soyuz TM-32, arrived at the station, and took over responsibilities as the station's lifeboat. The crew launched by Soyuz TM-32, which included the first paying space touristDennis Tito, were returned to Earth in May aboard Soyuz TM-31. The visiting mission of which Tito was apart is sometimes referred to as ISS EP-1.

The Soyuz carried a crew of three to dock it with the Zvezda module of the International Space Station (ISS) at about 09:21 UT on November 2. The Progress M1-3 cargo craft that was docked with Zvezda was released to make way for the Soyuz. The crew of two Russian and one American spent over three months on the ISS, and returned to Earth in an American shuttle (STS-102) in February 2001. In the initial days, the crew brought a variety of life support systems on-line, and created a lap-top computer network that helped run all systems in the ISS. The remaining months were allotted for exercise and space endurance practice. The crew was first group of a planned decade-long "permanent inhabitation" of the ISS.